Reviewed, UniProtKB/Swiss-Prot Q9UBU9 (NXF1_HUMAN)

Names and origin

Protein names

Recommended name:
    Nuclear RNA export factor 1
Alternative name(s):
    Tip-associating protein
    Tip-associated protein
    mRNA export factor TAP

Gene names

Name:	NXF1
Synonyms:	TAP

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	619 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Involved in the nuclear export of mRNA species bearing retroviral constitutive transport elements (CTE) and in the export of mRNA from the nucleus to the cytoplasm. Ref.7
Subunit structure	Interacts with NXT1, NXT2, E1B-AP5, RAE1, THOC4 and with several nucleoporins. Is part of the exon junction complex (EJC) containing NCBP1, NCBP2, RNPS1, RBM8A, SRRM1, NXF1, RENT1, RENT2, RENT3A, RENT3B, THOC4 and/or REFBP2. Found in a mRNA complex with RENT3A and RENT3B. Interacts with Saimiriine herpesvirus 2 TIP protein. Interacts with EIF4A3, NUPL2 and THOC4. Ref.6 Ref.8 Ref.12
Subcellular location	Nucleus › nucleoplasm. Nucleus speckle. Cytoplasm. Note: Localized predominantly in the nucleoplasm and at both the nucleoplasmic and cytoplasmic faces of the nuclear pore complex. Shuttles between the nucleus and the cytoplasm. Travels to the cytoplasm as part of the exon junction complex (EJC) bound to mRNA.
Tissue specificity	Expressed ubiquitously.
Domain	The minimal CTE binding domain consists of an RNP-type RNA binding domain (RBD) and leucine-rich repeats. The nucleoporin binding domain consists of a NTF2-like domain and a TAP domain (also called UBA-like domain). The NTF2 domain heterodimerizes with NXT1 and NXT2. The formation of NXF1/NXT1 heterodimers is required for NXF1-mediated nuclear mRNA export. The TAP domain mediates direct interactions with nucleoporin-FG-repeats and is necessary and sufficient for localization of NXF1 to the nuclear rim. The conserved loop 594-NWD-596 of the UBA domain has a critical role in the interaction with nucleoporins. The leucine-rich repeats and the NTF2-domain are essential for the export of mRNA from the nucleus.
Miscellaneous	The RNA-binding domain is a non-canonical RNP-type domain.
Sequence similarities	Belongs to the NXF family. Contains 4 LRR (leucine-rich) repeats. Contains 1 NTF2 domain. Contains 1 RRM (RNA recognition motif) domain. Contains 1 TAP-C domain.

Ontologies

Keywords
Biological process	Host-virus interaction Transport mRNA transport
Cellular component	Cytoplasm Nucleus
Domain	Leucine-rich repeat Repeat
Ligand	RNA-binding
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	interspecies interaction between organisms Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	nucleotide binding Inferred from electronic annotation. Source: InterPro protein binding Ref.6 Ref.19 Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
	P22575	3	EBI-398874,EBI-866709	From a different organism.
DHX9	Q08211	4	EBI-398874,EBI-352022
NXT1	Q9UKK6	1	EBI-398874,EBI-301889
SFRS1	Q07955	3	EBI-398874,EBI-398920
SFRS7	Q16629	1	EBI-398874,EBI-398885

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 619

619

Nuclear RNA export factor 1

PRO_0000220529

Regions

Domain

119 – 198

80

RRM

Repeat

266 – 291

26

LRR 1

Repeat

292 – 315

24

LRR 2

Repeat

316 – 343

28

LRR 3

Repeat

344 – 371

28

LRR 4

Domain

386 – 536

151

NTF2

Domain

565 – 619

55

TAP-C

Motif

67 – 100

34

Nuclear localization signal

Motif

83 – 110

28

Nuclear export signal

Compositional bias

551 – 561

11

Pro-rich

Experimental info

Mutagenesis

306 – 308

3

ERE → AAA: Decreases the export of mRNAs from the nucleus.

Mutagenesis

594

1

W → A: Suppresses FG-nucleoporin binding.

Mutagenesis

595

1

D → R: Suppresses FG-nucleoporin binding.

Mutagenesis

617

1

F → A: Suppresses FG-nucleoporin binding. Ref.21

Sequence conflict

119

1

W → C in AAB81111. Ref.6

Sequence conflict

256

1

T → N in AAD20016. Ref.3

Secondary structure

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619

Helix Strand Turn

Details...

Helix

132 – 142

11

Helix

173 – 175

3

Turn

176 – 178

3

Helix

206 – 218

13

Turn

222 – 224

3

Beta strand

226 – 228

3

Helix

232 – 234

3

Helix

236 – 240

5

Helix

250 – 263

14

Beta strand

269 – 271

3

Helix

280 – 285

6

Helix

286 – 289

4

Beta strand

295 – 297

3

Helix

306 – 312

7

Beta strand

318 – 321

4

Helix

326 – 330

5

Helix

334 – 344

11

Helix

381 – 398

18

Helix

403 – 408

6

Beta strand

410 – 419

10

Helix

433 – 436

4

Turn

442 – 444

3

Helix

448 – 454

7

Beta strand

455 – 458

4

Helix

459 – 466

8

Beta strand

472 – 474

3

Helix

476 – 478

3

Beta strand

480 – 486

7

Beta strand

491 – 501

11

Turn

505 – 508

4

Beta strand

510 – 521

12

Beta strand

525 – 538

14

Helix

541 – 548

8

Helix

565 – 578

14

Helix

582 – 591

10

Turn

592 – 594

3

Helix

596 – 608

13

Helix

614 – 617

4

Sequences

	Sequence		Length	Mass (Da)
	Q9UBU9-1 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: 338872AADA789FBF	FASTA	619	70,182
	10 20 30 40 50 60 MADEGKSYSE HDDERVNFPQ RKKKGRGPFR WKYGEGNRRS GRGGSGIRSS RLEEDDGDVA 70 80 90 100 110 120 MSDAQDGPRV RYNPYTTRPN RRGDTWHDRD RIHVTVRRDR APPERGGAGT SQDGTSKNWF 130 140 150 160 170 180 KITIPYGRKY DKAWLLSMIQ SKCSVPFTPI EFHYENTRAQ FFVEDASTAS ALKAVNYKIL 190 200 210 220 230 240 DRENRRISII INSSAPPHTI LNELKPEQVE QLKLIMSKRY DGSQQALDLK GLRSDPDLVA 250 260 270 280 290 300 QNIDVVLNRR SCMAATLRII EENIPELLSL NLSNNRLYRL DDMSSIVQKA PNLKILNLSG 310 320 330 340 350 360 NELKSERELD KIKGLKLEEL WLDGNSLCDT FRDQSTYISA IRERFPKLLR LDGHELPPPI 370 380 390 400 410 420 AFDVEAPTTL PPCKGSYFGT ENLKSLVLHF LQQYYAIYDS GDRQGLLDAY HDGACCSLSI 430 440 450 460 470 480 PFIPQNPARS SLAEYFKDSR NVKKLKDPTL RFRLLKHTRL NVVAFLNELP KTQHDVNSFV 490 500 510 520 530 540 VDISAQTSTL LCFSVNGVFK EVDGKSRDSL RAFTRTFIAV PASNSGLCIV NDELFVRNAS 550 560 570 580 590 600 SEEIQRAFAM PAPTPSSSPV PTLSPEQQEM LQAFSTQSGM NLEWSQKCLQ DNNWDYTRSA 610 QAFTHLKAKG EIPEVAFMK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"TAP binds to the constitutive transport element (CTE) through a novel RNA-binding motif that is sufficient to promote CTE-dependent RNA export from the nucleus." Braun I.C., Rohrbach E., Schmitt C., Izaurralde E. EMBO J. 18:1953-1965(1999) [PubMed: 10202158] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS. Tissue: Cervix carcinoma.
[2]	"The human Tap protein is a nuclear mRNA export factor that contains novel RNA-binding and nucleocytoplasmic transport sequences." Kang Y., Cullen B.R. Genes Dev. 13:1126-1139(1999) [PubMed: 10323864] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Identification of novel import and export signals of human TAP, the protein that binds to the constitutive transport element of the type D retrovirus mRNAs." Bear J., Tan W., Zolotukhin A.S., Tabernero C., Hudson E.A., Felber B.K. Mol. Cell. Biol. 19:6306-6317(1999) [PubMed: 10454577] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lung.
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain and Placenta.
[6]	"Tap: a novel cellular protein that interacts with tip of herpesvirus saimiri and induces lymphocyte aggregation." Yoon D.-W., Lee H., Seol W., DeMaria M., Rosenzweig M., Jung J.U. Immunity 6:571-582(1997) [PubMed: 9175835] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 61-619, INTERACTION WITH SAIMIRINE HERPESVIRUS 2 TIP. Tissue: Lymphocyte.
[7]	"TAP, the human homolog of Mex67p, mediates CTE-dependent RNA export from the nucleus." Grueter P., Tabernero C., von Kobbe C., Schmitt C., Saavedra C., Bachi A., Wilm M., Felber B.K., Izaurralde E. Mol. Cell 1:649-659(1998) [PubMed: 9660949] [Abstract] Cited for: FUNCTION.
[8]	"The Mex67p-mediated nuclear mRNA export pathway is conserved from yeast to human." Katahira J., Straesser K., Podtelejnikov A., Mann M., Jung J.U., Hurt E. EMBO J. 18:2593-2609(1999) [PubMed: 10228171] [Abstract] Cited for: INTERACTION WITH NUPL2.
[9]	"Overexpression of TAP/p15 heterodimers bypasses nuclear retention and stimulates nuclear mRNA export." Braun I.C., Herold A., Rode M., Conti E., Izaurralde E. J. Biol. Chem. 276:20536-20543(2001) [PubMed: 11259411] [Abstract] Cited for: CHARACTERIZATION.
[10]	"The C-terminal domain of TAP interacts with the nuclear pore complex and promotes export of specific CTE-bearing RNA substrates." Bachi A., Braun I.C., Rodrigues J.P., Pante N., Ribbeck K., von Kobbe C., Kutay U., Wilm M., Goerlich D., Carmo-Fonseca M., Izaurralde E. RNA 6:136-158(2000) [PubMed: 10668806] [Abstract] Cited for: CHARACTERIZATION.
[11]	"Prediction of structural domains of TAP reveals details of its interaction with p15 and nucleoporins." Suyama M., Doerks T., Braun I.C., Sattler M., Izaurralde E., Bork P. EMBO Rep. 1:53-58(2000) [PubMed: 11256625] [Abstract] Cited for: MUTAGENESIS.
[12]	"Magoh, a human homolog of Drosophila mago nashi protein, is a component of the splicing-dependent exon-exon junction complex." Kataoka N., Diem M.D., Kim V.N., Yong J., Dreyfuss G. EMBO J. 20:6424-6433(2001) [PubMed: 11707413] [Abstract] Cited for: INTERACTION WITH THOC4 AND THE EXON JUNCTION COMPLEX.
[13]	"Role of the nonsense-mediated decay factor hUpf3 in the splicing-dependent exon-exon junction complex." Kim V.N., Kataoka N., Dreyfuss G. Science 293:1832-1836(2001) [PubMed: 11546873] [Abstract] Cited for: IDENTIFICATION IN A MRNP COMPLEX WITH RENT3A AND RENT3B.
[14]	"Communication of the position of exon-exon junctions to the mRNA surveillance machinery by the protein RNPS1." Lykke-Andersen J., Shu M.-D., Steitz J.A. Science 293:1836-1839(2001) [PubMed: 11546874] [Abstract] Cited for: IDENTIFICATION IN A POST-SPLICING COMPLEX WITH RBM8A; RENT1; RENT2; RENT3A; RENT3B AND RNPS1.
[15]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[16]	"eIF4A3 is a novel component of the exon junction complex." Chan C.C., Dostie J., Diem M.D., Feng W., Mann M., Rappsilber J., Dreyfuss G. RNA 10:200-209(2004) [PubMed: 14730019] [Abstract] Cited for: INTERACTION WITH EIF4A3 AND THOC4.
[17]	"Assembly and mobility of exon-exon junction complexes in living cells." Schmidt U., Im K.-B., Benzing C., Janjetovic S., Rippe K., Lichter P., Wachsmuth M. RNA 15:862-876(2009) [PubMed: 19324961] [Abstract] Cited for: SUBCELLULAR LOCATION.
[18]	"The structure of the mRNA export factor TAP reveals a cis arrangement of a non-canonical RNP domain and an LRR domain." Liker E., Fernandez E., Izaurralde E., Conti E. EMBO J. 19:5587-5598(2000) [PubMed: 11060011] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 102-372.
[19]	"Structural basis for the recognition of a nucleoporin FG repeat by the NTF2-like domain of the TAP/p15 mRNA nuclear export factor." Fribourg S., Braun I.C., Izaurralde E., Conti E. Mol. Cell 8:645-656(2001) [PubMed: 11583626] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF COMPLEX WITH NXT1, X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF COMPLEX WITH NXT1-FG-REPEAT.
[20]	"Structural basis for the interaction between the Tap/NXF1 UBA domain and FG nucleoporins at 1A resolution." Grant R.P., Neuhaus D., Stewart M. J. Mol. Biol. 326:849-858(2003) [PubMed: 12581645] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.0 ANGSTROMS) OF 561-619 IN COMPLEX WITH RANBP3.
[21]	"Structure of the C-terminal FG-nucleoporin binding domain of Tap/NXF1." Grant R.P., Hurt E., Neuhaus D., Stewart M. Nat. Struct. Biol. 9:247-251(2002) [PubMed: 11875519] [Abstract] Cited for: STRUCTURE BY NMR OF 551-619, MUTAGENESIS OF PHE-617.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

AJ132712 mRNA. Translation: CAA10753.1.
AF112880 mRNA. Translation: AAD39102.1.
AF126246 mRNA. Translation: AAD20016.1.
AK027192 mRNA. No translation available.
BC004904 mRNA. Translation: AAH04904.1.
BC028041 mRNA. Translation: AAH28041.1.
U80073 mRNA. Translation: AAB81111.1.

IPI

IPI00033153.

RefSeq

NP_006353.2.

UniGene

Hs.523739
Hs.601546

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1FO1	X-ray	2.90	A/B	102-372	[»]
1FT8	X-ray	3.15	A/B/C/D/E	102-372	[»]
1GO5	NMR	-	A	551-619	[»]
1JKG	X-ray	1.90	B	371-619	[»]
1JN5	X-ray	2.80	B	371-619	[»]
1KOH	X-ray	3.80	A/B/C/D	96-372	[»]
1KOO	X-ray	3.80	A/B/C/D	96-372	[»]
1OAI	X-ray	1.00	A	561-619	[»]
2Z5K	X-ray	2.60	B	53-82	[»]
2Z5M	X-ray	3.00	B	53-82	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9UBU9. 8 interactions.

Protein family/group databases

TCDB

3.A.18.1.1. nuclear mRNA exporter (mRNA-E) family.

PTM databases

PhosphoSite

Q9UBU9.

Proteomic databases

PeptideAtlas

Q9UBU9.

PRIDE

Q9UBU9.

Genome annotation databases

Ensembl

ENSG00000162231. Homo sapiens. [Contig view]

GeneID

10482.

UCSC

uc001nvf.1. human.

Organism-specific databases

GeneCards

GC11M062316.

H-InvDB

HIX0009727.

HGNC

HGNC:8071. NXF1.

HPA

CAB016327.

MIM

602647. gene.

PharmGKB

PA31858.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

Q9UBU9.

HOVERGEN

Q9UBU9.

OMA

Q9UBU9. YDKSWLL.

Enzyme and pathway databases

Reactome

REACT_125. Processing of Capped Intron-Containing Pre-mRNA.
REACT_71. Gene Expression.

Gene expression databases

ArrayExpress

Q9UBU9.

Bgee

Q9UBU9.

CleanEx

HS_NXF1.

GermOnline

ENSG00000162231. Homo sapiens.

Family and domain databases

InterPro

IPR012677. a_b_plait_nuc_bd.
IPR001611. Leu-rich_rpt.
IPR002075. NTF2.
IPR018222. Nuclear_transport_factor_2_euk.
IPR005637. TAP_C.
IPR015245. Tap_RNA_bd.
IPR003603. U2A'_phosphoprotein32A_C.
[Graphical view]

Gene3D

G3DSA:3.30.70.330. a_b_plait_nuc_bd. 1 hit.

Pfam

PF00560. LRR_1. 1 hit.
PF02136. NTF2. 1 hit.
PF09162. Tap-RNA_bind. 1 hit.
PF03943. TAP_C. 1 hit.
[Graphical view]

SMART

SM00446. LRRcap. 1 hit.
SM00804. TAP_C. 1 hit.
[Graphical view]

PROSITE

PS50177. NTF2_DOMAIN. 1 hit.
PS50102. RRM. False negative.
PS51281. TAP_C. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

39766.

SOURCE

Search...

Entry information

Entry name

NXF1_HUMAN

Accession

Primary (citable) accession number: Q9UBU9
Secondary accession number(s): Q99799, Q9UQL2

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 27, 2002
Last sequence update:	May 1, 2000
Last modified:	July 7, 2009
This is version 105 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)